Metformin use in pregnancy: What about long-term effects in offspring?

Metformin use in pregnancy is increasing worldwide. Unlike insulin, metformin crosses the placenta. Consequently, maternal and fetal concentrations are comparable. Teratogenic effects are not reported, nor are adverse pregnancy outcomes. Reduced risk of hypertensive disorders, hypoglycemia, and macrosomia are potential benefits, together with lower gestational weight gain. Although metformin has been prescribed for pregnant women during the last 40 years, long-term data regarding offspring outcomes are still lacking. Independent of maternal glycemic control, recent meta-analyses report lower birthweight but accelerated postnatal growth and higher body mass index in metformin-exposed children. The longest follow-up study of placebo-controlled metformin exposure in utero found an increased prevalence of central adiposity and obesity among children 5-10 years old. Recently, a Danish study reported a threefold increased risk of genital anomalies in boys, whose fathers used metformin around the time of conception. This commentary addresses the current controversies on metformin use in pregnancy.